CRISPR/Cas9-mediated Disruption of Fibroblast Growth Factor 5 in Rabbits Results in a Systemic Long Hair Phenotype by Prolonging Anagen.

Hair growth and morphology are generally regulated by the hair cycle in mammals. Fibroblast Growth Factor 5 (FGF5), which is a hair cycle regulator, has a role in regulating the hair cycle during the transition from the anagen phase to the catagen phase, and a hereditary long hair phenotype has been widely reported when is mutated in humans and other species. However, there has been no such report in rabbits. Thus, the first exon of rabbit was disrupted by the CRISPR/Cas9 system, and the phenotype of rabbits was characterized while using hematoxylin and eosin (H&E) staining, immunohistochemistry, quantitative PCR, scanning electron microscopy, and western blotting. The results showed a significant and systemic long hair phenotype in the rabbits, which indicated that is a negative regulator of hair growth. In addition, a decreased diameter of the fiber and a higher area proportion of hair follicle clusters were determined in rabbits as compared with the WT rabbits. Further investigation verified that prolonging the anagen phase in rabbits, with decreased BMP2/4 pathway signaling and increased VERSICAN pathway signaling, caused the systemic long hair phenotype. Taken together, these results indicate a systemic long hair phenotype by prolonging anagen in rabbits, which could be widely used for Fur production and an ideal model for studying the mechanism of long hair in the future.